Rare variants in SLC5A10 are associated with serum 1,5-anhydroglucitol (1,5-AG) in the Atherosclerosis Risk in Communities (ARIC) Study
Open accessAbstract
Serum 1,5-anhydroglucitol (1,5-AG) is an emerging biomarker used to monitor glycemic control in persons with diabetes. We performed whole-exome sequencing, examining the association between rare, coding genetic variants and 1,5-AG among European ancestry (N = 6,589) and African ancestry (N = 2,309) participants without diagnosed diabetes in the Atherosclerosis Risk in Communities (ARIC) Study. Five variants representing 3 independent signals on chromosome 17 in SLC5A10, a glucose transporter not previously known to transport 1,5-AG, were associated with 1,5-AG levels up to 10.38 µg/mL lower per allele (1,5-AG range 3.4–32.8 µg/mL) in the European ancestry sample and validated in the African ancestry sample. Together these variants explained 6% of the variance in 1,5-AG. Two of these variants (rs61741107, p = 8.85E-56; rs148178887, p = 1.13E-36) were rare, nonsynonymous, and predicted to be damaging or deleterious by multiple algorithms. Gene-based SKAT-O analysis supported these results (SLC5A10 p = 5.13E-64 in European ancestry, validated in African ancestry, p = 0.006). Interestingly, these novel variants are not associated with other biomarkers of hyperglycemia or diabetes (p > 0.2). The large effect sizes and protein-altering, multiple independent signals suggest SLC5A10 may code for an important transporter of 1,5-AG in the kidney, with a potential nonglucose-related effect on 1,5-AG, impacting its clinical utility as a diabetes biomarker in this subpopulation.
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Slc5a10 is a glucose transporter gene associated with atherosclerosis risk.
“Slc5a10 is a glucose transporter gene associated with atherosclerosis risk35.”
From Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice (2021) · cites this paper as [35]
The Discussion identifies SLC5A10 as a glucose transporter. The Abstract reports an association between SLC5A10 variants and serum 1,5-AG in the Atherosclerosis Risk in Communities study, not an association with atherosclerosis risk. No page numbers are provided in our copy. (LLM, conf=0.88)
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References 25 · Cited by 12
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- Authors
- Loomis, S. J., Köttgen, A., Li, M., Tin, A., Coresh, J., Boerwinkle, E., Gibbs, R., Muzny, D., Pankow, J., Selvin, E., & Duggal, P.
- Affiliations
- Johns Hopkins University (US)
- The University of Texas Health Science Center at Houston (US)
- Baylor College of Medicine (US)
- University of Minnesota (US)
- Corresponding author
- Duggal, Priya
- ORCID
- Venue
- Scientific Reports
- Published
- 2019-04-11
- Volume
- 9
- Issue
- 1
- Pages
- 5941-5941
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6459884
- OpenAlex
- W2940127709
- Cited by
- 12
- References
- 25
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (T32 HL007024)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (K24DK106414, R01DK089174)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- 1,5-anhydroglucitol, rare variants, glucose transporters, diabetes mellitus, kidney, African ancestry, European ancestry, hyperglycemia, SKAT-O
- MeSH terms
- Exome Sequencing, Deoxyglucose, Female, Humans, Longitudinal Studies, Male, Middle Aged, Risk Factors, Polymorphism, Single Nucleotide, Atherosclerosis, Sodium-Glucose Transport Proteins
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